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Publications (56) View all
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Article: Negative life stress and longitudinal hippocampal volume changes in older adults with and without depression.
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ABSTRACT: Major depressive disorder is associated with smaller hippocampal volumes but the mechanisms underlying this relationship are unclear. To examine the effect of environmental influences, we examined the relationship between self-reported stressors and two-year change in hippocampal volume. Seventy elderly nondepressed subjects and eighty-nine elderly depressed subjects were followed for two years. The number of negative stressful life events (nSLE), perceived stress levels, and cranial MRI were obtained at baseline and at the two-year assessment. For secondary analyses, subjects provided blood for 5-HTTLPR polymorphism genotyping. After controlling for covariates including presence or absence of depression, greater numbers of baseline nSLEs were significantly associated with greater baseline hippocampal volumes bilaterally. Greater numbers of baseline nSLEs were also associated with reduction in hippocampal volume over two years in the right but not the left hemisphere. Neither perceived stress levels nor changes in stress measures were significantly associated with hippocampal volume measures. However, in secondary analyses, we found that increases in perceived stress over time was associated with volume reduction of the left hippocampus, but only in 5-HTTLPR L/L homozygotes. Our findings suggest different short- and long-term effects of negative life stressors on hippocampal volumes in older adults. These effects appear independent on the presence or absence of depression. Furthermore, these effects may be moderated by genetic polymorphisms in key neurotransmitter systems. These novel findings have important implications for understanding environmental influences on brain aging.Journal of psychiatric research 03/2013; · 3.72 Impact Factor -
Article: AGTR1 gene variation: association with depression and frontotemporal morphology.
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ABSTRACT: The renin-angiotensin system (RAS) is implicated in the response to physiological and psychosocial stressors, but its role in stress-related psychiatric disorders is poorly understood. We examined if variation in AGTR1, the gene coding for the type 1 angiotensin II receptor (AT(1)R), is associated with a diagnosis of depression and differences in white matter hyperintensities and frontotemporal brain volumes. Participants comprised 257 depressed and 116 nondepressed elderly Caucasian subjects who completed clinical assessments and provided blood samples for genotyping. We used a haplotype-tagging single nucleotide polymorphism (htSNP) analysis to test for variation in AGTR1. For measurement of hyperintense lesions, 1.5 Tesla magnetic resonance imaging (MRI) data were available on 33 subjects. For measurements of the hippocampus and dorsolateral prefrontal cortex (dlPFC), 3 Tesla MRI data were available on 70 subjects. Two htSNPs exhibited statistically significant frequency differences between diagnostic cohorts: rs10935724 and rs12721331. Although hyperintense lesion volume did not significantly differ by any htSNP, dlPFC and hippocampus volume differed significantly for several htSNPs. Intriguingly, for those htSNPs differing significantly for both dlPFC and hippocampus volume, the variant associated with smaller dlPFC volume was associated with larger hippocampal volume. This supports the idea that genetic variation in AGTR1 is associated with depression and differences in frontotemporal morphology.Psychiatry Research 06/2012; 202(2):104-9. · 2.52 Impact Factor -
Article: Stressful life events, perceived stress, and 12-month course of geriatric depression: direct effects and moderation by the 5-HTTLPR and COMT Val158Met polymorphisms.
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ABSTRACT: Although the relation between stressful life events (SLEs) and risk of major depressive disorder is well established, important questions remain about the effects of stress on the course of geriatric depression. Our objectives were (1) to examine how baseline stress and change in stress is associated with course of geriatric depression and (2) to test whether polymorphisms of serotonin transporter (5-HTTLPR) and catechol-O-methyltransferase (COMT Val158Met) genes moderate this relation. Two-hundred and sixteen depressed subjects aged 60 years or older were categorized by remission status (Montgomery-Asberg depression rating scale≤6) at 6 and 12 months. At 6 months, greater baseline numbers of self-reported negative and total SLEs and greater baseline perceived stress severity were associated with lower odds of remission. At 12 months, only baseline perceived stress predicted remission. When we examined change in stress, 12-month decrease in negative SLEs and level of perceived stress were associated with improved odds of 12-month remission. When genotype data were included, COMT Val158Met genotype did not influence these relations. However, when compared with 5-HTTLPR L/L homozygotes, S allele carriers with greater baseline numbers of negative SLEs and with greater decrease in negative SLEs were more likely to remit at 12 months. This study demonstrates that baseline SLEs and perceived stress severity may influence the 12-month course of geriatric depression. Moreover, changes in these stress measures over time correlate with depression outcomes. 5-HTTLPR S carriers appear to be more susceptible to both the effects of enduring stress and the benefit of interval stress reduction.Stress (Amsterdam, Netherlands) 11/2011; 15(4):425-34. · 3.21 Impact Factor -
Article: Amygdala volume in late-life depression: relationship with age of onset.
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ABSTRACT: Depression is common in the elderly population. Although numerous neuroimaging studies have examined depressed elders, there is limited research examining how amygdala volume may be related to depression. A cross-sectional examination of amygdala volume comparing elders with and without a diagnosis of major depressive disorder, and between depressed subjects with early and later initial depression onset. An academic medical center. Ninety-one elderly patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depression (54 early-onset depressed and 37 late-onset depressed) and 31 elderly subjects without any psychiatric diagnoses. Amygdala and cerebral volumes were measured using reliable manual tracing methods. In models controlling for age, sex, and cerebral volume, there was a significant difference between diagnostic cohorts in amygdala volume bilaterally (left: F[2, 116] = 16.28, p < 0.0001; right: F[2, 116] = 16.28, p < 0.0001). Using least squares mean group analyses, both early- and late-onset depressed subjects exhibited smaller bilateral amygdala volumes than did the nondepressed cohort (all comparisons p < 0.0001), but the two depressed cohorts did not exhibit a statistically significant difference. Limitations include missing antidepressant treatment data, recall bias, inability to establish a causal relationship between amygdala size and depression given the cross-sectional nature of the design. Depression in later life is associated with smaller amygdala volumes, regardless of age of initial onset of depression.The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 09/2011; 19(9):771-6. · 3.35 Impact Factor -
Article: Reduction of dorsolateral prefrontal cortex gray matter in late-life depression.
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ABSTRACT: Postmortem studies have documented abnormalities in the dorsolateral prefrontal cortex (dlPFC) in depressed subjects. In this study we used magnetic resonance imaging to test for dlPFC volume differences between older depressed and non-depressed individuals. Eighty-eight subjects meeting DSM IV criteria for major depressive disorder and thirty-five control subjects completed clinical evaluations and cranial 3T magnetic resonance imaging. After tissue types were identified using an automated segmentation process, the dlPFC was measured in both hemispheres using manual delineation based on anatomical landmarks. Depressed subjects had significantly lower gray matter in the left and right dorsolateral prefrontal cortex (standardized to cerebral parenchyma) after controlling for age and sex. Our study confirmed the reduction of dorsolateral prefrontal cortex in elderly depressed subjects, especially in the gray matter. These regional abnormalities may be associated with psychopathological changes in late-life depression.Psychiatry Research 07/2011; 193(1):1-6. · 2.52 Impact Factor
